Intravaginal washing agent

ABSTRACT

An intravaginal washing agent by which the self-cleaning effect in the vagina of a patient suffering from a vaginal infection such as bacterial vaginosis, cervical chlamydiosis, trichomonal vaginitis or candidal vaginitis can be restored in the home, the invasion of bacteria, fungi, protozoa, etc. into the vagina can be prevented, and invading organisms can be exterminated. This intravaginal washing agent, which can be easily handled, has no toxicity and exhibits excellent effects, comprises a fermented soybean milk obtained by fermenting soybean milk by coculturing a plural number of lactic acid bacteria or an extract obtained by extracting the fermented soybean milk with an alcohol, in particular, over 6 month or longer.

TECHNICAL FIELD

The present invention relates to a washing agent to wash the vagina of apatient suffering from a vaginal infection such as bacterial vaginosis,chlamydial cervicitis, trichomonal vaginitis, or candidal vaginitis, thewashing agent also being effective as a curative medicine, and tomedical care and pharmaceutical technology.

BACKGROUND ART

A large number of fungi of the genus lactic acid bacillus such asDoderlein's bacillus reside in the vagina of healthy adult women whomenstruate. The presence of these lactic acid bacilli maintains thehealthy balance of bacteria in the vagina and prevents the reproductiveorgan from being infected by pathogenic microbes.

The lactic acid bacillus is reproduced using glycogen secreted from thevaginal mucosa as an energy source and competes with external pathogensto protect the vaginal cavity from attack by other bacteria. However,because of the recent development of a large number of antibiotics,pharmaceutical preparations of such antibiotics have often been used,causing the lactic acid bacilli in the vagina to be eliminated.

As a result, a large number of infected anaerobic bacteria such asBacteroides, Peptostreptococcus, Peptococcus, and Mobiluncus G.vaginalis are reproduced in the vagina and interaction between thesebacteria causes the development of bacterial vaginitis. Also, theinfection of Trichomonas vaginalis or Candida (all of the above Candidaalbicans) causes the development of vaginitis.

Sulfonamides, antibiotics, and antibacterial agents are chiefly used tocure the above diseases. However, there is a concern that theadministration of such antibiotics causes side effects such as rash,pruritus, local reddening, inflammation, and erosion. The administrationof such antibiotics also leads to the death of the lactic acid bacilliindwelling in the vagina. Furthermore, since some pathogenic bacteria(for example, Staphylococcus) acquire resistance to the antibiotics, ithas been difficult to cure such diseases by administering antibiotics.

Japanese Unexamined Patent Application Publication No. 11-322621discloses the use of lactic acid bacillus such as Lactobacillus casei,Lactobacillus gasseri, Lactobacillus fermintum, Lactobacillus caseisubs. Pseudoplantarum, and Lactobacillus crispatus to cure vaginalinfections. This seems to be based on an idea that the lactic acidbacillus is used to replenish the dead bacilli.

Because of the overuse of antibiotics, the decrease in the immunesystem's function, and the increase in sexual behavior, the number ofwomen suffering from a disease such as bacterial vaginosis, chlamydialcervicitis, trichomonal vaginitis, or candidal vaginitis has beenincreasing. Many women are reluctant to visit a gynecologist for such adisease and the symptoms are often aggravated.

In order to improve such a situation, the present inventor hasconsidered the known art, developed a washing agent, and performedstudies so that the patient can cure the disease by herself, in otherwords, the patient can wash the vagina by herself. The patient canrecover the self-cleaning effect in the vagina using this washing agentin the home. The washing agent prevents bacteria, fungi, and protozoa,etc. from invading into the vagina and sterilizes the invadingmicroorganisms. The washing agent can be easily handled, has notoxicity, and exhibits excellent effects.

As a result, the present inventor has found that substances generallyproduced and secreted by lactic acid bacteria (hereinafter referred toas an extract of fermentation solution of lactic acid bacteria), whichhave an effect of improving the condition of intestinal microorganisms,and which are commercially available, solve the above problems. Thepresent inventor has also found that the above substances can be used asan excellent washing agent of the vagina for a woman suffering frombacterial vaginosis, chlamydial cervicitis, trichomonal vaginitis, orcandidal vaginitis, and the above substances are effective as a curativemedicine for such a vaginal infection. Thus, the present inventor hasaccomplished the present invention.

DISCLOSURE OF INVENTION

The invention described in claim 1 of the present invention provides

an intravaginal washing agent composed of fermented soybean milkproduced by fermenting soybean milk with a co-culture of a plurality oflactic acid bacteria.

The invention described in claim 2 of the present invention provides

an intravaginal washing agent composed of an extract produced byextracting fermented soybean milk with an alcohol, the fermented soybeanmilk being produced by fermenting soybean milk with a co-culture of aplurality of lactic acid bacteria.

The invention described in claim 3 of the present invention provides

the intravaginal washing agent composed of an extract produced by thefollowing process. The process includes the steps of sterilizing thefermented soybean milk produced by fermenting soybean milk with aco-culture of a plurality of lactic acid bacteria, adding an alcohol tothe fermented soybean milk, and performing the extraction with thealcohol for at least six months.

The invention described in claim 4 of the present invention provides

the intravaginal washing agent composed of an extract produced byextracting fermented soybean milk with an alcohol, the fermented soybeanmilk being produced by fermenting soybean milk with a co-culture of aplurality of lactic acid bacteria,

wherein the extract includes a total content of at least 20% of aningredient of which the retention time measured by liquid chromatographyunder the following conditions is at least 10 minutes.

Measurement conditions for liquid chromatography

-   -   Column: Asahipak GS=220H    -   Mobile phase: 100 mM sodium phosphate buffer    -   Flow rate: 1.0 /min.    -   Column temperature: 40° C.

The invention described in claim 5 of the present invention provides

the intravaginal washing agent composed of an extract produced byextracting fermented soybean milk with an alcohol, the fermented soybeanmilk being produced by fermenting soybean milk with a co-culture of aplurality of lactic acid bacteria,

wherein the extract includes a total content of at least 25% of aningredient of which the retention time measured by liquid chromatographyunder the following conditions is at least 7 minutes.

Measurement conditions for liquid chromatography

-   -   Column: Asahipak GS=220H    -   Mobile phase: 100 mM sodium phosphate buffer    -   Flow rate: 1.0 /min.    -   Column temperature: 40° C.

The invention described in claim 6 of the present invention provides

the intravaginal washing agent composed of an extract produced byextracting fermented soybean milk with an alcohol, the fermented soybeanmilk being produced by fermenting soybean milk with a co-culture of aplurality of lactic acid bacteria,

wherein the extract includes a total content of at least 25% of aningredient of which the retention time measured by liquid chromatographyunder the following conditions is at least 7 minutes, and a totalcontent of at least 20% of an ingredient of which the retention timemeasured by liquid chromatography under the following conditions is atleast 10 minutes.

Measurement conditions for liquid chromatography

-   -   Column: Asahipak GS=220H    -   Mobile phase: 100 mM sodium phosphate buffer    -   Flow rate: 1.0 /min.    -   Column temperature: 40° C.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a chart from a liquid chromatograph of an extract offermentation solution of lactic acid bacteria according to the presentinvention.

BEST MODE FOR CARRYING OUT THE INVENTION

An intravaginal washing agent according to the present inventionincludes fermented soybean milk as the active ingredient. The fermentedsoybean milk is produced by fermenting soybean milk with a co-culture ofa plurality of lactic acid bacteria, preferably, for about 100 to about300 hours. This fermented soybean milk itself can be used as theintravaginal washing agent in the present invention.

More specifically, examples of the active ingredient of the intravaginalwashing agent include a substance containing an extract of fermentedsoybean milk and other various impurities, and a solid or a liquidprepared by solid-liquid separation and containing the extract offermented soybean milk. In order to utilize the extract of fermentedsoybean milk effectively, the extract used as the effective ingredientis preferably extracted with an organic solvent. More preferably, theextract is produced by extracting fermented soybean milk with analcohol, the fermented soybean milk being produced with a co-culture ofa plurality of lactic acid bacteria.

It is known that substances generally produced and secreted by lacticacid bacteria, which are contained in fermented soybean milk produced byfermentation with a co-culture (hereinafter referred to as fermentedsoybean milk extract), have a superior advantage for human health. Inaddition, many products containing such substances are commerciallyavailable.

The fermented soybean milk extract in the present invention is obtainedfrom fermented soybean milk produced by fermenting soybean milk with aco-culture of a plurality of lactic acid bacteria, and in particular, isobtained by extracting the fermented soybean milk with an alcohol. Theconditions for the extraction with an alcohol are as follows:

-   (1) The alcohol is preferably ethanol because the fermented soybean    milk extract is used as a food. An approximately equivalent amount    of ethanol is added to the fermented soybean milk, and the fermented    soybean milk is extracted.-   (2) Sterilized fermented soybean milk is used for the extraction.    Examples of the sterilization method include heat sterilization and    sterilization by disrupting the bacterial cells.

Although the extraction may be performed with heating, the extraction ispreferably performed at normal temperature to prevent thermaldenaturation. In addition, the extraction is preferably performed in acool, dark place to prevent the long-term influence of light.

It is expected that the extraction at normal temperature proceeds at alow speed. In order to produce a superior extract from the fermentedsoybean milk, the extraction is performed for a long time, generally forat least 6 months, and preferably at least 1 year. Taking such a longtime provides a superior fermented soybean milk extract.

Fermented soybean milk produced by fermentation with a co-culture of aplurality of lactic acid bacteria is sterilized, and an alcohol is thenadded to the fermented soybean milk. The extraction is performed for atleast 6 months. As will be clarified in the following Examples, thisprocess provides the following fermented soybean milk extract and alsoincreases the kind of the ingredient. The fermented soybean milk extractincludes a total content of at least 20%, preferably at least 25%, of aningredient of which the retention time measured by liquid chromatographyunder a specific condition is at least 10 minutes.

The ingredient is defined in more detail as follows:

The fermented soybean milk extract includes a total content of at least25%, preferably at least 30%, of an ingredient of which the retentiontime measured by liquid chromatography is at least 7 minutes; or thefermented soybean milk extract includes a total content of at least 25%,preferably at least 30%, of an ingredient of which the retention timemeasured by liquid chromatography is at least 7 minutes and a totalcontent of at least 20%, preferably at least 25%, of an ingredient ofwhich the retention time measured by liquid chromatography is at least10 minutes.

As the extraction is performed for a long time, the amount of eachingredient in the fermented soybean milk extract gradually increases.However, since the long-term extraction decreases the extraction effectand decreases the efficiency of the extraction operation, a fermentedsoybean milk extract generally containing each ingredient up to 40% andup to 35%, preferably containing up to 35% and up to 30% is used.

In order to clean the vaginal walls, the fermented soybean milk or theextract thereof that is the intravaginal washing agent of the presentinvention can be used as follows without further treatment or it can bediluted. The fermented soybean milk or the extract thereof may beapplied on the pudendum. For example, gauze soaked with the fermentedsoybean milk or the extract thereof may be applied on the affected area.Furthermore, the fermented soybean milk or the extract thereof may beintroduced and dispersed in the vagina with a dropping pipette, and acotton ball or a tampon may then be inserted for some time.

The fermented soybean milk or the extract thereof in the presentinvention does not impose a strict limitation on the quantity applied,and can be freely used, because it is widely ingested as a healthmaintenance food and does not cause side effects. Therefore, theintravaginal washing agent of the present invention may be usedeveryday, every other day, or every few days. As a result, the use ofthe intravaginal washing agent cleans the inside of the vagina toalleviate or terminate the symptoms of, for example, bacterialvaginosis, chlamydial cervicitis, trichomonal vaginitis, or candidalvaginitis.

EXAMPLES

The intravaginal washing agent of the present invention will now bedescribed in more detail with reference to the Examples.

Example 1

<Preparation Extract of Fermentation Solution>

As shown in the following Table 1, lactic acid bacteria and yeast thatform combinations of four kinds and four groups were prepared. In thetable, symbols A, B, 1, 2, 3, and 4 represent that the strain isdifferent. TABLE 1 (1) (2) (3) (4) I B. bulgaricus A B. acidophilus 1.Micrococcus lactisacidi 1. Yeast 1. II B. bulgaricus B B. acidophilus 2.Micrococcus lactisacidi 2. Yeast 2. III Kornchenbacillus A B.acidophilus 3. Micrococcus lactisacidi 3. Yeast 3. IV Kornchenbacillus BB. acidophilus 4. Micrococcus lactisacidi 4. Yeast 4.

The lactic acid bacteria in each group were separately cultured for 48hours using soybean milk as the culture medium, while the temperaturewas gradually increased from 20° C. to 40° C.

After the culture was performed for 48 hours, the culture solutions weretransferred to one container. The mixture was further cultured for 96hours, while the temperature was gradually increased from 20° C. to 40°C.

The fermented soybean milk prepared by completing the culture wassterilized by heating. Subsequently, an equivalent amount of alcohol wasadded to the solution. The mixture was kept in the cool and dark placefor one year to perform the extraction.

The extracted fermented soybean milk was filtered and subjected tosolid-liquid separation to prepare a clear light yellow fermentedsoybean milk extract I.

The resultant extract of fermentation solution was analyzed by liquidchromatography under the following conditions. Table 2 and FIG. 1 showthe results.

Measurement conditions for liquid chromatography

-   -   Column: Asahipak GS=220H    -   Mobile phase: 100 mM sodium phosphate buffer    -   Flow rate: 1.0/min.    -   Column temperature: 40° C.    -   Detector: Ultraviolet spectrophotometer

Detection wavelength: 210 nm TABLE 2 ingredient retention time areaheight concentration 1 5.194 8974013 71553 37.8998 2 6.815 7031508 7311229.6960 3 9.382 1118511 19495 4.7238 4 10.521 559947 14058 2.3648 512.199 2181670 17105 9.2138 6 14.993 908867 7338 3.8384 7 18.435 4456153782 1.8820 8 21.474 362632 4422 1.5315 9 23.559 1158857 10852 4.8942 1026.911 237078 2011 1.0012 11 29.886 358612 2975 1.5145 12 32.622 3409702516 1.4400 total 23678272 229218 100.0000

<Confirmatory Test of Cleaning Effect-1>

After written informed consent was obtained from seven femaleoutpatients (19 years old to 29 years old) who visited a gynecologistcomplaining of an increase in vaginal discharge and an unpleasant odortherefrom, 1 cc of the above extract of fermentation solution was evenlydispersed on the vaginal walls with a dropping pipette under the directobservation of the inside of the vagina. Subsequently, a cotton ballsterilized by high pressure was inserted in the vagina. Four hourslater, the cotton ball was removed by the patients.

When the intravaginal cleaning was performed, vaginal discharge in thevagina was collected to check for Chlamydia, Trichomonas, and Candida.Patients who were negative for Chlamydia, Trichomonas, and Candida, andhad vaginal discharge that was yellow and had an amine-like odor wereclinically diagnosed as having bacterial vaginosis. Among the sevenpatients, five women were diagnosed with bacterial vaginosis, one womanwas diagnosed with chlamydial cervicitis, and one woman was diagnosedwith candidal vaginitis.

The cleaning effects in the patients were as follows. The duration ofthe test was March to April in 2002.

(1) Patient (A.M.) 20 Years Old, Bacterial vaginosis

March 28, First cleaning, A large amount of yellow vaginal discharge,Strong odor

March 30, Second cleaning, Both the vaginal discharge and the odor weresomewhat decreased. (Two days after the first cleaning)

April 6, Third cleaning, Both the vaginal discharge and the odor wereimproved by 100%. (Eight days after the first cleaning)

April 9, Fourth cleaning, The condition in which both the vaginaldischarge and the odor were improved by 100% was maintained.

(2) Patient (F.Y.) 29 Years Old, Bacterial vaginosis

April 9, First cleaning, A large amount of yellow vaginal discharge,Strong odor

April 11, Second cleaning, Remained the same, (Two days after the firstcleaning)

April 13, Third cleaning, Both the vaginal discharge and the odor wereimproved by 50%. (Four days after the first cleaning)

April 15, Fourth cleaning, The condition in which both the vaginaldischarge and the odor were improved by 50% was maintained.

(3) Patient (Y.E.) 19 Years Old, Bacterial vaginosis

April 9, First cleaning, A large amount of yellow vaginal discharge,Strong odor

April 11, Second cleaning, The vaginal discharge and the odor remainedthe same, (Two days after the first cleaning)

April 15, Third cleaning, The vaginal discharge was decreased by 30%,and the odor was improved by 40%.

(4) Patient (Y.C.) 24 Years Old, Bacterial vaginosis

March 8, First cleaning, A large amount of yellow vaginal discharge,Strong odor

March 12, Second cleaning, Both the vaginal discharge and the odor weresomewhat decreased. (Four days after the first cleaning)

March 15, Third cleaning, The vaginal discharge was improved by 50%, andthe odor was improved by 100%.

March 22, Fourth cleaning, The condition in which the vaginal dischargewas improved by 50% and the odor was improved by 100% was maintained.

(5) Patient (K.H.) 29 Years Old, Bacterial vaginosis

March 5, First cleaning, A large amount of yellow vaginal discharge,Strong odor

March 11, Second cleaning, Both the vaginal discharge and the odor weresomewhat decreased. (Six days after the first cleaning)

March 14, Third cleaning, The vaginal discharge and the odor werefurther improved. (Nine days after the first cleaning)

March 22, Fourth cleaning, Both the vaginal discharge and the odor wereimproved by 100%.

(6) Patient (M.S.) 21 Years Old, Chlamydial cervicitis

April 6, First cleaning, A large amount of yellow vaginal discharge,Strong odor

April 8, Second cleaning, Both the vaginal discharge and the odor weresomewhat decreased. (Two days after the first cleaning)

April 9, Third cleaning, The vaginal discharge was improved by 40%, andthe odor was improved by 100%.

April 12, Fourth cleaning, The condition in which the vaginal dischargewas improved by 40% and the odor was improved by 100% was maintained.

(7) Patient (S.M.) 27 Years Old, Candidal vaginitis

March 8, First cleaning, A large amount of white vaginal discharge

March 11, Second cleaning, The vaginal discharge was somewhat decreased.(Three days after the first cleaning)

March 14, Third cleaning, The vaginal discharge was decreased by 80%.(Six days after the first cleaning)

April 15, Fourth cleaning, The condition in which both the vaginaldischarge and the odor were improved by 50% was maintained.

<Confirmatory Test of Cleaning Effect-2>

The following symptoms were tested by outpatients who mainly complainedof vaginal discharge with an unpleasant odor.

-   1. Gray vaginal discharge-   2. pH in the vagina>4.5 (5.0)-   3. Detection of an amine-like odor-   4. Detection of a clue cell (at least 20% of the epithelial cells)

Among 30 patients who were positive for the three items out of the abovesymptoms, 23 patients who could visit the hospital for treatment for oneweek were selected. After written informed consent was obtained from thepatients, the above-mentioned extract of fermentation solution wasadministered in the vagina. On the other hand, Chlomy (registeredtrademark) vaginal tablets (chloramphenicol vaginal tablets) wereadministered to seven patients who could not visit the hospital.

The degree of the unpleasant odor and the vaginal discharge wasevaluated by the test subjects as outpatients using a visual analogscale (VAS).

Table 3 shows the evaluation results of the patients to whom the extractof fermentation solution was administered. Table 4 shows the evaluationresults of the patients to whom Chlomy vaginal tablets wereadministered. The evaluation showed the following results.

-   (1) In the patient group to whom the extract of fermentation    solution was administered in the vagina, one week after the    administration, the degree of the unpleasant odor and the vaginal    discharge was significantly decreased (P<0.001 and P<0.001,    respectively), compared with that before the administration.-   (2) In the patient group to whom Chlomy vaginal tablets were    administered, one week after the administration, the degree of the    unpleasant odor and the vaginal discharge was significantly    decreased (P=0.0016 and P=0.0018, respectively), compared with that    before the administration.-   (3) The change in the degree of the unpleasant odor and the vaginal    discharge (decreasing ratio ‰) was represented by formula [(before    administration−after administration)/before administration]. In the    above decreasing ratio, there was no statistically significant    difference between the group to whom the extract of fermentation    solution was dministered in the vagina and the group to whom Chlomy    aginal tablets were administered.

4) In conclusion, the administration of the fermentation solutionextract in the vagina had the same curative effect as that of Chlomyvaginal tablets and caused no side effects. TABLE 3 one week later firstexamination discharge/ odor/ vaginal unpleasant decreasing decreasingpatient age discharge odor rate(%) rate(%) 1 20 100 95 22/78 18/81  2 3575 79 23/69 38/52  3 25 60 84 21/65 0/100 4 25 64 64 18/72 6/91  5 35 7648 31/59 19/60  6 24 33 70  4/88 6/91  7 22 75 79 23/69 38/52  8 20 10030 22/78 26/13  9 20 100 95 22/78 18/81  10 21 43 42  3/93 0/100 11 1854 67  0/100 0/100 12 28 70 91 46/34 61/33  13 20 54 67  0/100 0/100 1421 52 65  0/100 0/100 15 25 72 21 21/71 5/76  16 25 62 65  0/100 0/10017 25 60 84  0/100 0/100 18 38 60 63  0/100 0/100 19 27 61 64 12/800/100 20 20 72 76  0/100 0/100 21 21 54 67 22/59 0/100 22 25 76 48 0/100 0/100 23 37 54 49  4/93 4/92 

TABLE 4 one week later first examination discharge/ odor/ vaginalUnpleasant decreasing decreasing patient Age discharge odor rate(%)rate(%) 1 23 73 65 12/84 10/84 2 28 91 70 21/77 42/40 3 22 79 75 14/8211/85 4 18 47 55 17/64 34/38 5 37 100 71  0/100 23/68 6 33 64 75 15/7745/40 7 21 58 50 43/26 34/32 8 21 91 92  1/99  0/100

INDUSTRIAL APPLICABILITY

Ingredients in fermented soybean milk produced by fermenting soybeanmilk with a co-culture of a plurality of lactic acid bacteria,particularly in the above fermented soybean milk extract have beenidentified to a certain degree. Although nucleic acids, amino acids, andvitamins are listed as the ingredients, some ingredients are stillunknown.

The following function of the extract of fermented soybean milk isknown: The extract of fermented soybean milk improves the condition ofintestinal microorganisms and helps, for example, the synthesis ofhormones, the synthesis of vitamins and enzymes, metabolism ofcholesterol, blood sugar regulation, and blood pressure homeostasis. Inaddition, the extract of fermented soybean milk is effective againsthepatitis, chronic arthritis, atopic dermatitis, angina pectoris, andvarious cancers. However, only a few pharmacologic effects arespecifically confirmed under the present situation. At present, themechanism of action of the effects in the present invention is also notknown.

However, as shown in the above clinical results, the fermented soybeanmilk or the extract thereof that is the intravaginal washing agent ofthe present invention is an effective medical agent (washing agent)against bacterial vaginosis, chlamydial cervicitis, and candidalvaginitis, and in addition, the effect works immediately. About threedays after the administration, the symptoms were clearly improved andthis condition was maintained. Even when the interval of theadministration was one week or more, the effect could be maintained.Thus, the fermented soybean milk or the extract thereof is a superiormedical agent.

These advantages are significantly excellent, compared with a knowntablet of lactic acid bacteria having an effective ratio of about 60%and a known yogurt containing lactic acid bacteria having an effectiveratio of about 50%, the yogurt causing incongruity or discomfort whenused as a washing agent. When the curative effect was finally assessed30 days later, the fermented soybean milk or the extract thereof hadexcellent effects, compared with, for example, lactic acid produced bylactic acid bacteria. In this case, there was also a significantdifference in the improvement in the surface of the skin.

In addition, the fermented soybean milk or the extract thereof that isthe intravaginal washing agent in the present invention had the samecurative effect as that of commercially available Chlomy vaginal tabletsand had no side effects.

As clearly described above, the substances generally produced andsecreted by lactic acid bacteria (hereinafter referred to as an extractof fermentation solution of lactic acid bacteria), which have an effectof improving the condition of intestinal microorganisms, and which arecommercially available, can be used as an excellent washing agent of thevagina of a woman suffering from bacterial vaginosis, chlamydialcervicitis, trichomonal vaginitis, or candidal vaginitis. Furthermore,the above substances are effective as a curative medicine for such avaginal infection. These substances can be widely used in the field ofmedical care, such as in medicines and pharmaceuticals.

1. An intravaginal washing agent comprising: fermented soybean milkproduced by fermenting soybean milk with a co-culture of a plurality oflactic acid bacteria.
 2. An intravaginal washing agent comprising: anextract produced by extracting fermented soybean milk with an alcohol,the fermented soybean milk being produced by fermenting soybean milkwith a co-culture of a plurality of lactic acid bacteria.
 3. Theintravaginal washing agent according to claim 2, wherein the extractionwith an alcohol is performed by adding an alcohol to the sterilizedfermented soybean milk and is performed for at least six months.
 4. Theintravaginal washing agent according to claim 2 or claim 3, wherein theextract includes a total content of at least 20% of an ingredient ofwhich the retention time measured by liquid chromatography under thefollowing conditions is at least 10 minutes. Measurement conditions forliquid chromatography Column: Asahipak GS=220H Mobile phase: 100 mMsodium phosphate buffer Flow rate: 1.0/min. Column temperature: 40° C.5. The intravaginal washing agent according to claim 2 or claim 3,wherein the extract includes a total content of at least 25% of aningredient of which the retention time measured by liquid chromatographyunder the following conditions is at least 7 minutes. Measurementconditions for liquid chromatography Column: Asahipak GS=220H Mobilephase: 100 mM sodium phosphate buffer Flow rate: 1.0/min. Columntemperature: 40° C.
 6. The intravaginal washing agent according to claim2 or claim 3, wherein the extract includes a total content of at least25% of an ingredient of which the retention time measured by liquidchromatography under the following conditions is at least 7 minutes, anda total content of at least 20% of an ingredient of which the retentiontime measured by liquid chromatography under the following conditions isat least 10 minutes. Measurement conditions for liquid chromatographyColumn: Asahipak GS=220H Mobile phase: 100 mM sodium phosphate bufferFlow rate: 1.0/min. Column temperature: 40° C.